# Nociceptive Afferent Topographical Innervation of the Heart and Stomach

> **NIH NIH U01** · UNIVERSITY OF CENTRAL FLORIDA · 2021 · $459,679

## Abstract

More than 50 million Americans suffer from chronic pain. Of those, 25 million live with daily chronic pain
and lack effective and safe non-opioid options for pain management. In particular, the new incidence of chest
pain is 15.5 per 1000 person-years, which is highly related to coronary heart disease and heart failure. In
addition, the prevalence of chronic abdominal pain is around 22.9 per 1,000 person-years. A large percentage
of abdominal pain is related to the gastrointestinal tract (GI). However, the anatomical and physiological
mechanisms of peripheral nociceptive processes have not been well studied. In this study, we aim to perform a
comprehensive anatomical mapping of pain-related neural circuitry in two visceral organs: heart (Aim 1) and
stomach (Aim 2). Nociception, from these organs in mammals, is mainly mediated by sensory neurons in the
spinal dorsal root ganglia (DRG) and to a lesser extent in the vagal nodose-jugular ganglion complex (for short:
nodose ganglion, seen below). Previously, Dr. Powley’s group and Dr. Cheng’s group have studied vagal
afferent and efferent as well as sympathetic efferent innervations of the heart and stomach, and their different
types of terminal structures (taxonomy) in whole mounts of atria and the stomach. To do so, we used a
combination of techniques, including tracer injections, anterograde tracing of axon distributions and terminal
structures, and microscopic imaging. However, the study of specific nociceptive nerve topographical
innervation in the heart and stomach is not well studied because such elegant, powerful, and challenging
techniques above have not yet been well applied in the spinal DRG. In this study, we will inject different tracers
into the DRG (left or right: C7-T5 for Heart; left or right: T6-T12 for Stomach) and into the vagal nodose
ganglia (left or right: for both Heart and Stomach) for anterograde labeling of sensory nerve innervation. In
addition, we will also use immunohistochemical (IHC) labeling of CGRP, SP, and TRPV1 (the three nociceptive
nerve markers) in tracer-injected animals that will specifically identify the nociceptive afferent innervation of
these organs from distinct origins (spinal, vagal, or left/right side). The topographical innervation map will be
annotated and presented in the 3D reconstructed heart and stomach, and then their 3D scaffolds of these
organs (Aim 3). We will also assess for organ specificity (nociceptive innervation that distinguishes the heart
and stomach from each other), left or right sidedness of ganglia, and sex differences. Comprehensive and
topographical mapping of nociceptive afferent innervation of these organs will substantially improve the
understanding of physiological processes in relation to nociception. This mapping data will also aid to develop
new selective interventional therapies/stimulations for visceral pain of these organs.

## Key facts

- **NIH application ID:** 10263240
- **Project number:** 5U01NS113867-03
- **Recipient organization:** UNIVERSITY OF CENTRAL FLORIDA
- **Principal Investigator:** ZIXI Jack CHENG
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $459,679
- **Award type:** 5
- **Project period:** 2019-09-19 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10263240

## Citation

> US National Institutes of Health, RePORTER application 10263240, Nociceptive Afferent Topographical Innervation of the Heart and Stomach (5U01NS113867-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10263240. Licensed CC0.

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